Efficacy of antipsychotic treatment in schizophrenia: results after 24 months in Italian patients in the Schizophrenia Outpatient Health Outcomes (SOHO) study Efficacia della terapia antipsicotica per la schizofrenia: risultati a 24 mesi dello studio SOHO

Summary Objectives Aim of the present study was to examine the outcomes associated with antipsychotic treatment over a 24-month timeframe for Italian patients taking part in the Schizophrenia Outpatient Health Outcomes (SOHO) study. Methods SOHO is a prospective Results A large number of patients (2,533) continued treatment for 24 months with the antipsychotic started at baseline. The CGI-overall score improved from baseline after continuous treatment for 6, 12, 18 and 24 months in all treatment groups (Fig. 2). Compared with olanzapine, there was significantly less improvement in the CGI-overall score for the other antipsychotic groups, except clozapine. Likewise, quality of life improved in all treatment groups in all epochs, and there was a significantly greater improvement in EQ-VAS with olanzapine compared with risperidone and oral typicals (Fig. 3) . Social functioning also improved in all treatment groups, but more patients had social activities in the olanzapine group than in the clozapine group (after 6, 12 and 18 months continuous treatment) or typical antipsychotic groups (oral typical: after 6 and 12 months; depot typical: after 6 months continuous treatment) (Tab. V). Olanzapine, clozapine and quetiapine were associated with less EPS after treatment in all four epochs (Tab. VI). Olanzapine and clozapine were associated with higher average weight gain Conclusion

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits

ABSTRACT Ketamine is a rapidly acting antidepressant in patients with treatment-resistant depression (TRD). Although the mechanisms underlying these effects are not fully established, inquiry to date has focused on the triggering of synaptogenesis transduction pathways via glutamatergic mechanisms. Preclinical data suggest that blockade of metabotropic glutamate (mGlu2/3) receptors shares many overlapping features and mechanisms with ketamine and may also provide rapid efficacy for TRD patients. Central dopamine circuitry is recognized as an end target for mood regulation and hedonic valuation and yet has been largely neglected in mechanistic studies of antidepressant-relevant effects of ketamine. Herein, we evaluated the changes in dopaminergic neurotransmission after acute administration of ketamine and the mGlu2/3 receptor antagonist LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid ] in preclinical models using electrophysiologic, neurochemical, and behavioral endpoints. When given acutely, both ketamine and LY341495, but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increased the number of spontaneously active dopamine neurons in the ventral tegmental area (VTA), increased extracellular levels of dopamine in the nucleus accumbens and prefrontal cortex, and enhanced the locomotor stimulatory effects of the dopamine D 2/3 receptor agonist quinpirole. Further, both ketamine and LY341495 reduced immobility time in the tail-suspension assay in CD1 mice, which are relatively resistant to SSRI antidepressants. Both the VTA neuronal activation and the antidepressant phenotype induced by ketamine and LY341495 were attenuated by the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-(9CI)-benzo[f]quinoxaline-7-sulfonamide, indicating AMPA-dependent effects. These findings provide another overlapping mechanism of action of ketamine and mGlu2/3 receptor antagonism that differentiates them from conventional antidepressants and thus support the potential rapidly acting antidepressant actions of mGlu2/3 receptor antagonism in patients